Our primary goals are to assess the influence of the social environment on susceptibility to upper respiratory illness and to identify the pathways through which environmental factors "get under the skin" to influence disease expression. We hypothesize that the social environment influences behavior, hypothalamic-pituitary-adrenocortical (HPA) and autonomic nervous system (ANS) responses which in turn influence the regulation of both cellular and humoral immune response to the virus. We use a unique prospective design. We first assess characteristics of the social environment and the status of behavioral and physiological systems we predict to link these characteristics to host resistance in 260 healthy adults who are seronegative for antibodies to the challenge virus. Subsequently, we expose each subject by intranasal drops to one of two strains of rhinovirus and monitor them closely for evidence of infection and illness in a cloistered environment. Measures of illness collected immediately before and daily during the cloister include virus shedding and titer, nasal pro-inflammatory, anti-inflammatory and anti-viral cytokine production, nasal and general symptoms, body temperature, nasal secretion production and nasal mucociliary clearance function. Using these data, we will determine if the social environment influences illness expression by altering baseline cellular immune status (delayed type hypersensitivity), Th-1/Th-2 cytokine balance, and the ability to produce pro-inflammatory cytokines (from mitogen stimulated peripheral blood mononuclear cells);whether it influences the regulation of cytokine production in response to the infection;and whether the association between the social environment and immunity are mediated by the ANS (separating sympathetic and parasympathetic contributions) and/or HPA systems. All analyses will control for demographic factors and will focus on whether the social environment predicts clinical illness (verified infection + clinical diagnosis). The results of this study will define the pathways by which one's social environment influences their susceptibility to upper respiratory virus infection and may identify potential targets for behavioral or pharmaceutical interventions to restore disease resistance in persons most at risk because of their social environments.